Autoantibodies typical of non-organ-specific autoimmune diseases in HIV-seropositive patients

Muller, Sylviane; Richalet, Pascale; Laurent-Crawford, Anne G.; Barakat, S.; Rivière, Yves; Porrot, Françoise; Chamaret, S.; Briand, Jean‐Paul; Montagnier, Luc; Hovanessian, Ara G.

doi:10.1097/00002030-199209000-00004

Cited by 78 publications

(41 citation statements)

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“…First, the low CD4 counts in one donor, "case 5," originally classified as having ICL solely on the basis of two CD4 counts Ͻ 300/mm 3 , returned to normal after treatment of an M. tuberculosis infection, and this donor, as two others with stable low CD4 counts, showed no evidence for apoptosis at any level of absolute CD4 cell count. Second, we detected antihistone autoantibodies, presumably induced by fragmented chromatin, in some of these sera, with reactivity predominantly to type H2B, a pattern identical to that found in HIV disease (12,36) and simian immunodeficiency virus infection in macaques (37), both of which have been associated with CD4ϩ T cell apoptosis: in vitro in the case of HIV (10,11), and in vivo in macaques (37). Third, detection of apoptosis among CD8ϩ T cells appeared to correlate with their depletion in vivo, occurring in those ICL patients with low levels of both CD4ϩ and CD8ϩ T cells.…”

Section: Discussionsupporting

confidence: 60%

Apoptotic depletion of CD4+ T cells in idiopathic CD4+ T lymphocytopenia.

Laurence

Mitra²,

Steiner³

et al. 1996

J. Clin. Invest.

103

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Progressive loss of CD4 ؉ T lymphocytes, accompanied by opportunistic infections characteristic of the acquired immune deficiency syndrome, has been reported in the absence of any known etiology. The pathogenesis of this syndrome, a subset of idiopathic CD4 ؉ T lymphocytopenia (ICL), is uncertain. We report that CD4 ؉ T cells from seven of eight ICL patients underwent accelerated programmed cell death, a process facilitated by T cell receptor cross-linking. Apoptosis was associated with enhanced expression of Fas and Fas ligand in unstimulated cell populations, and partially inhibited by soluble anti-Fas mAb. In addition, apoptosis was suppressed by aurintricarboxylic acid, an inhibitor of calcium-dependent endonucleases and proteases, in cells from four of seven patients. The in vivo significance of these findings was supported by three factors: the absence of accelerated apoptosis in persons with stable, physiologic CD4 lymphopenia without clinical immune deficiency; detection of serum antihistone H2B autoantibodies, one consequence of DNA fragmentation, in some patients; and its selectivity, with apoptosis limited to the CD4 population in some, and occurring among CD8 ϩ T cells predominantly in those individuals with marked depletion of both CD4 ؉ and CD8 ؉ peripheral T lymphocyte subsets. These data suggest that patients with idiopathic loss of CD4 ؉ T lymphocytes linked to clinical immune suppression have evidence for accelerated T cell apoptosis in vitro that may be pathophysiologic and amenable to therapy with apoptosis inhibitors. ( J. Clin. Invest. 1996. 97:672-680.)

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Section: Discussionsupporting

confidence: 60%

Apoptotic depletion of CD4+ T cells in idiopathic CD4+ T lymphocytopenia.

Laurence

Mitra²,

Steiner³

et al. 1996

J. Clin. Invest.

103

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“…Interestingly, among such patients anti-dsDNA antibodies are detected by ELISA (43) or by the Crithidia test (unpublished observations). Polyomavirus reactivations may therefore explain development of anti-DNA antibodies generally, and not exclusively for SLE patients.…”

Section: Observations)mentioning

confidence: 93%

Experimental expression in mice and spontaneous expression in human SLE of polyomavirus T-antigen. A molecular basis for induction of antibodies to DNA and eukaryotic transcription factors.

Rekvig¹,

Moens²,

Sundsfjord³

et al. 1997

J. Clin. Invest.

109

151

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“…Especially in HIV-infected children a constant polyclonal B cell activation may lead to B cell expansion and elevated Lg levels (Lane et al, 1985;Via and Shearer, 1989). The antibody response is not only directed against viral proteins, such as gp120, gp41 and p24, but also against self antigens such as CD4 and MHC (Golding et al, 1988;Via and Shearer, 1989;Muller et al, 1992). Antibodies against gp41 have been shown to crossreact with MHC class II antigens and crossreactivity has been explained by a sequence identity of seven aminoacids between gp41 and MHC class II molecules (Blackburn et al, 1991).…”

Section: Introductionmentioning

confidence: 99%

Anti-CD95 (APO-1/Fas) autoantibodies and T cell depletion in human immunodeficiency virus Type 1 (HIV-1)-infected children

et al. 1998

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Advanced stages of HIV-1-infection are characterized by progressive CD4 + T cell depletion. Peripheral T cells from HIV-1 + donors show accelerated apoptosis in vitro. The CD95 (APO-1/Fas) receptor/ligand system is involved in this process. To further study deregulation of the CD95 system in peripheral T cells during HIV-1-infection, we measured CD95-expression on CD4 + and CD8 + T cells together with serum levels of soluble CD95 (sCD95) and anti-CD95 autoantibodies in HIV-1 + children and healthy controls. Anti-CD95 levels in HIV-1 + children were significantly elevated when compared to uninfected controls, whereas serum levels of sCD95 were not different. In HIV-1 + children, CD95-expression on CD4 + and CD8 + T cells increased with age. A strong correlation between depletion of CD4 + cells in vivo and increase in CD95-expression on CD4 + T cells was observed. In contrast, such a correlation was not found for CD8 + T cells. A negative correlation between anti-CD95 autoantibody levels and CD4 + T cell counts, that was predicted by multiple linear regression analysis of pooled data, was found in individual patients observed longitudinally by repeated measurements. Since anti-CD95 autoantibodies isolated from HIV-infected adults have previously been shown to induce apoptosis of sensitive target cells in vitro, we speculate that the interaction of these antibodes with CD95-positive and CD95-sensitive T cells in vivo might be involved in progressive T cell loss during HIV-1-infection.

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Autoantibodies typical of non-organ-specific autoimmune diseases in HIV-seropositive patients

Cited by 78 publications

References 0 publications

Apoptotic depletion of CD4+ T cells in idiopathic CD4+ T lymphocytopenia.

Apoptotic depletion of CD4+ T cells in idiopathic CD4+ T lymphocytopenia.

Experimental expression in mice and spontaneous expression in human SLE of polyomavirus T-antigen. A molecular basis for induction of antibodies to DNA and eukaryotic transcription factors.

Anti-CD95 (APO-1/Fas) autoantibodies and T cell depletion in human immunodeficiency virus Type 1 (HIV-1)-infected children

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